SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation

Jaecheol Lee, Ning Yi Shao, David T. Paik, Haodi Wu, Hongchao Guo, Vittavat Termglinchan, Jared M. Churko, Youngkyun Kim, Tomoya Kitani, Ming Tao Zhao, Yue Zhang, Kitchener D. Wilson, Ioannis Karakikes, Michael P. Snyder, Joseph C. Wu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation. SETD7 associates with different co-factors at these stages, including SWI/SNF chromatin-remodeling factors during mesodermal formation and the transcription factor NKX2.5 in cardiac progenitors to drive their differentiation. Further analyses revealed that SETD7 binds methylated H3K36 in the bodies of its target genes to facilitate RNA polymerase II (Pol II)-dependent transcription. Moreover, abnormal SETD7 expression impairs functional attributes of terminally differentiated cardiomyocytes. Together, these results reveal how SETD7 acts at sequential steps in cardiac lineage commitment, and they provide insights into crosstalk between dynamic epigenetic marks and chromatin-modifying enzymes. Wu and colleagues define SETD7 as a key regulator of cardiac lineage commitment. SETD7 regulates the expression of lineage-specific target genes and interacts with various co-factors during cardiomyocyte differentiation. SETD7 associates with H3K36me3 histone modification, which is required for the transcriptional activation.

Original languageEnglish (US)
Pages (from-to)428-444.e5
JournalCell Stem Cell
Volume22
Issue number3
DOIs
StatePublished - Mar 1 2018
Externally publishedYes

Fingerprint

Cardiac Myocytes
Transcriptional Activation
Epigenomics
Histone Code
Genes
Chromatin Assembly and Disassembly
RNA Polymerase II
Chromatin Immunoprecipitation
Methyltransferases
Enzymes
Chromatin
Reading
Transcription Factors

Keywords

  • cardiomyocyte
  • epigenetics
  • H3K36 methylation
  • histone modification
  • lineage commitment
  • SETD7
  • stem cell
  • transcriptional regulation

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

Cite this

Lee, J., Shao, N. Y., Paik, D. T., Wu, H., Guo, H., Termglinchan, V., ... Wu, J. C. (2018). SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation. Cell Stem Cell, 22(3), 428-444.e5. https://doi.org/10.1016/j.stem.2018.02.005

SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation. / Lee, Jaecheol; Shao, Ning Yi; Paik, David T.; Wu, Haodi; Guo, Hongchao; Termglinchan, Vittavat; Churko, Jared M.; Kim, Youngkyun; Kitani, Tomoya; Zhao, Ming Tao; Zhang, Yue; Wilson, Kitchener D.; Karakikes, Ioannis; Snyder, Michael P.; Wu, Joseph C.

In: Cell Stem Cell, Vol. 22, No. 3, 01.03.2018, p. 428-444.e5.

Research output: Contribution to journalArticle

Lee, J, Shao, NY, Paik, DT, Wu, H, Guo, H, Termglinchan, V, Churko, JM, Kim, Y, Kitani, T, Zhao, MT, Zhang, Y, Wilson, KD, Karakikes, I, Snyder, MP & Wu, JC 2018, 'SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation', Cell Stem Cell, vol. 22, no. 3, pp. 428-444.e5. https://doi.org/10.1016/j.stem.2018.02.005
Lee, Jaecheol ; Shao, Ning Yi ; Paik, David T. ; Wu, Haodi ; Guo, Hongchao ; Termglinchan, Vittavat ; Churko, Jared M. ; Kim, Youngkyun ; Kitani, Tomoya ; Zhao, Ming Tao ; Zhang, Yue ; Wilson, Kitchener D. ; Karakikes, Ioannis ; Snyder, Michael P. ; Wu, Joseph C. / SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation. In: Cell Stem Cell. 2018 ; Vol. 22, No. 3. pp. 428-444.e5.
@article{735d3a754c934d1aaa4ff2b2697295ef,
title = "SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation",
abstract = "Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation. SETD7 associates with different co-factors at these stages, including SWI/SNF chromatin-remodeling factors during mesodermal formation and the transcription factor NKX2.5 in cardiac progenitors to drive their differentiation. Further analyses revealed that SETD7 binds methylated H3K36 in the bodies of its target genes to facilitate RNA polymerase II (Pol II)-dependent transcription. Moreover, abnormal SETD7 expression impairs functional attributes of terminally differentiated cardiomyocytes. Together, these results reveal how SETD7 acts at sequential steps in cardiac lineage commitment, and they provide insights into crosstalk between dynamic epigenetic marks and chromatin-modifying enzymes. Wu and colleagues define SETD7 as a key regulator of cardiac lineage commitment. SETD7 regulates the expression of lineage-specific target genes and interacts with various co-factors during cardiomyocyte differentiation. SETD7 associates with H3K36me3 histone modification, which is required for the transcriptional activation.",
keywords = "cardiomyocyte, epigenetics, H3K36 methylation, histone modification, lineage commitment, SETD7, stem cell, transcriptional regulation",
author = "Jaecheol Lee and Shao, {Ning Yi} and Paik, {David T.} and Haodi Wu and Hongchao Guo and Vittavat Termglinchan and Churko, {Jared M.} and Youngkyun Kim and Tomoya Kitani and Zhao, {Ming Tao} and Yue Zhang and Wilson, {Kitchener D.} and Ioannis Karakikes and Snyder, {Michael P.} and Wu, {Joseph C.}",
year = "2018",
month = "3",
day = "1",
doi = "10.1016/j.stem.2018.02.005",
language = "English (US)",
volume = "22",
pages = "428--444.e5",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "3",

}

TY - JOUR

T1 - SETD7 Drives Cardiac Lineage Commitment through Stage-Specific Transcriptional Activation

AU - Lee, Jaecheol

AU - Shao, Ning Yi

AU - Paik, David T.

AU - Wu, Haodi

AU - Guo, Hongchao

AU - Termglinchan, Vittavat

AU - Churko, Jared M.

AU - Kim, Youngkyun

AU - Kitani, Tomoya

AU - Zhao, Ming Tao

AU - Zhang, Yue

AU - Wilson, Kitchener D.

AU - Karakikes, Ioannis

AU - Snyder, Michael P.

AU - Wu, Joseph C.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation. SETD7 associates with different co-factors at these stages, including SWI/SNF chromatin-remodeling factors during mesodermal formation and the transcription factor NKX2.5 in cardiac progenitors to drive their differentiation. Further analyses revealed that SETD7 binds methylated H3K36 in the bodies of its target genes to facilitate RNA polymerase II (Pol II)-dependent transcription. Moreover, abnormal SETD7 expression impairs functional attributes of terminally differentiated cardiomyocytes. Together, these results reveal how SETD7 acts at sequential steps in cardiac lineage commitment, and they provide insights into crosstalk between dynamic epigenetic marks and chromatin-modifying enzymes. Wu and colleagues define SETD7 as a key regulator of cardiac lineage commitment. SETD7 regulates the expression of lineage-specific target genes and interacts with various co-factors during cardiomyocyte differentiation. SETD7 associates with H3K36me3 histone modification, which is required for the transcriptional activation.

AB - Cardiac development requires coordinated and large-scale rearrangements of the epigenome. The roles and precise mechanisms through which specific epigenetic modifying enzymes control cardiac lineage specification, however, remain unclear. Here we show that the H3K4 methyltransferase SETD7 controls cardiac differentiation by reading H3K36 marks independently of its enzymatic activity. Through chromatin immunoprecipitation sequencing (ChIP-seq), we found that SETD7 targets distinct sets of genes to drive their stage-specific expression during cardiomyocyte differentiation. SETD7 associates with different co-factors at these stages, including SWI/SNF chromatin-remodeling factors during mesodermal formation and the transcription factor NKX2.5 in cardiac progenitors to drive their differentiation. Further analyses revealed that SETD7 binds methylated H3K36 in the bodies of its target genes to facilitate RNA polymerase II (Pol II)-dependent transcription. Moreover, abnormal SETD7 expression impairs functional attributes of terminally differentiated cardiomyocytes. Together, these results reveal how SETD7 acts at sequential steps in cardiac lineage commitment, and they provide insights into crosstalk between dynamic epigenetic marks and chromatin-modifying enzymes. Wu and colleagues define SETD7 as a key regulator of cardiac lineage commitment. SETD7 regulates the expression of lineage-specific target genes and interacts with various co-factors during cardiomyocyte differentiation. SETD7 associates with H3K36me3 histone modification, which is required for the transcriptional activation.

KW - cardiomyocyte

KW - epigenetics

KW - H3K36 methylation

KW - histone modification

KW - lineage commitment

KW - SETD7

KW - stem cell

KW - transcriptional regulation

UR - http://www.scopus.com/inward/record.url?scp=85042367520&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042367520&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2018.02.005

DO - 10.1016/j.stem.2018.02.005

M3 - Article

C2 - 29499155

AN - SCOPUS:85042367520

VL - 22

SP - 428-444.e5

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 3

ER -